OBJECTIVE: To elucidate factors which affect the capacity of hematopoietic stem cells and monocytes of the spleen to proliferate, home to bone and differentiate into both osteoclasts and macrophages. METHODS: 1. A reproducible method for obtaining pure samples of stem cells and monocytes from normal and osteopetrotic stem cells will be employed. The bone resorbing-restorative activity (BRA) of these cells will be tested using appropriate recipients as described in previous investigations employing infusions of mixed populations of spleen cells (Science 190:784, 785, 1975 and J. Exp. Med. 142:651, 1975). 2. By various electron microscopic cyto- and immuno-chemical techniques the purified samples of stem cells and monocytes will be characterized. 3. Various chemical substances will be introduced into cultures of isolated pure populations of stem cells and monocytes in order to identify those substances which influence differentiation into osteoclasts or macrophages, proliferation and homing ability.